PMID- 17549730
OWN - NLM
STAT- MEDLINE
DCOM- 20071212
LR  - 20220227
IS  - 0360-4012 (Print)
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 85
IP  - 11
DP  - 2007 Aug 15
TI  - Progesterone increases brain-derived neuroptrophic factor expression and protects 
      against glutamate toxicity in a mitogen-activated protein kinase- and 
      phosphoinositide-3 kinase-dependent manner in cerebral cortical explants.
PG  - 2441-9
AB  - The higher prevalence and risk for Alzheimer's disease in women relative to men 
      has been partially attributed to the precipitous decline in gonadal hormone 
      levels that occurs in women following the menopause. Although considerable 
      attention has been focused on the consequence of estrogen loss, and thus 
      estrogen's neuroprotective potential, it is important to recognize that the 
      menopause results in a precipitous decline in progesterone levels as well. In 
      fact, progesterone is neuroprotective, although the precise mechanisms involved 
      remain unclear. Based on our previous observation that progesterone elicits the 
      phosphorylation of ERK and Akt, key effectors of the neuroprotective 
      mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI3-K) 
      pathways, respectively, we determined whether activation of either of these 
      pathways was necessary for progesterone-induced protection. With organotypic 
      explants (slice culture) of the cerebral cortex, we found that progesterone 
      protected against glutamate-induced toxicity. Furthermore, these protective 
      effects were inhibited by either the MEK1/2 inhibitor UO126 or the PI3-K 
      inhibitor LY294002, supporting the requirement for both the MAPK and PI3-K 
      pathways in progesterone-induced protection. In addition, at a concentration and 
      duration of treatment consistent with our neuroprotection data, progesterone also 
      increased the expression of brain-derived neurotrophic factor (BDNF), at the 
      level of both protein and mRNA. This induction of BDNF may be relevant to the 
      protective effects of progesterone, in that inhibition of Trk signaling, with 
      K252a, inhibited the protective effects of progesterone. Collectively, these data 
      suggest that progesterone is protective via multiple and potentially related 
      mechanisms. (c) 2007 Wiley-Liss, Inc.
CI  - Copyright 2007 Wiley-Liss, Inc.
FAU - Kaur, Paramjit
AU  - Kaur P
AD  - Department of Pharmacology and Neuroscience and the Institute for Aging and 
      Alzheimer's Disease Research, The Center FOR HER, University of North Texas 
      Health Science Center, Fort Worth, Texas 76107-2699, USA.
FAU - Jodhka, Parmeet K
AU  - Jodhka PK
FAU - Underwood, Wendy A
AU  - Underwood WA
FAU - Bowles, Courtney A
AU  - Bowles CA
FAU - de Fiebre, Nancyellen C
AU  - de Fiebre NC
FAU - de Fiebre, Christopher M
AU  - de Fiebre CM
FAU - Singh, Meharvan
AU  - Singh M
LA  - eng
GR  - P01 AG022550/AG/NIA NIH HHS/United States
GR  - AG26672/AG/NIA NIH HHS/United States
GR  - R21 AG026672/AG/NIA NIH HHS/United States
GR  - R03 AG023330/AG/NIA NIH HHS/United States
GR  - AG23330/AG/NIA NIH HHS/United States
GR  - R01 NS054687/NS/NINDS NIH HHS/United States
GR  - R01 NS054651-01A2/NS/NINDS NIH HHS/United States
GR  - AG22550/AG/NIA NIH HHS/United States
GR  - R01 NS054651/NS/NINDS NIH HHS/United States
GR  - R01 NS054687-01A2/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Cerebral Cortex/drug effects/*metabolism
MH  - Enzyme Activation/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Glutamic Acid/toxicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinases/drug effects/*metabolism
MH  - Neurons/drug effects/metabolism
MH  - Organ Culture Techniques
MH  - Phosphatidylinositol 3-Kinases/drug effects/*metabolism
MH  - Progesterone/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sex Factors
MH  - Signal Transduction/*physiology
PMC - PMC2693123
MID - NIHMS78917
EDAT- 2007/06/06 09:00
MHDA- 2007/12/13 09:00
PMCR- 2009/06/09
CRDT- 2007/06/06 09:00
PHST- 2007/06/06 09:00 [pubmed]
PHST- 2007/12/13 09:00 [medline]
PHST- 2007/06/06 09:00 [entrez]
PHST- 2009/06/09 00:00 [pmc-release]
AID - 10.1002/jnr.21370 [doi]
PST - ppublish
SO  - J Neurosci Res. 2007 Aug 15;85(11):2441-9. doi: 10.1002/jnr.21370.